Creating Business Advantages in the Biopharmaceutical Industry

An Executive Interview with Waters Corporation

Mike Harrington, VP of Waters Corporation's European Operations, looks at the company's unique approach to new technology development for an evolving industry.

“The application of this technology has saved companies millions of dollars in preventing the waste of valuable product”
-Mike Harrington, Waters Corporation

NGP: Traditional big pharma and biotech companies alike are facing funding issues and increasing competition, and to be successful companies have needed to refocus and reduce costs. How has Waters responded to the changing face of the pharmaceutical business?
MH: Critically – we listen to our customers. We have focused on designing systems to address the specific needs of the marketplace. In the biotherapeutics arena, for example, our customers have specific questions they need to answer relating to the character and quality of their biopharmaceuticals. Our analytical systems incorporate the tools that will allow them to answer these questions quickly and efficiently using software that is designed specifically for the task. This gives us a unique advantage as other providers are offering tools designed for proteomics experiments that often are not applicable in biopharmaceutical laboratories. However, creating business advantages for our customers is a multifaceted task and also involves helping them to reduce overhead, maximise system up-time, adopt efficient workflows, and promote improved visibility of information across their organisation. At Waters, we are committed to helping our customers adapt and accomplish their goals during these challenging times.

NGP: As pharmaceutical companies increase their focus on biotherapeutic development, their analytical needs will change. Can you tell us about the issues your customers are facing and describe where Waters has been active in addressing these needs?
MH: As firms increase their investment in biopharmaceutical development, we are seeing a widespread need for re-training of staff and the introduction of new technologies and approaches to drug development. We are working closely with academic and government institutions to promote education and training in this field. However, the need to drive new research with innovative, ‘breakthrough’ technology is where Waters is making a really significant contribution, particularly in the area of characterisation.

The need to fully characterise biopharmaceuticals is complicated by their inherent complexity and the need to identify structural variants. However, characterisation has improved significantly with the development of modern analytical technologies that provide accurate mass measurement of compounds and sub-structures. We understand the primary structure of these large molecules far better than ever before - and now - with the commercial development of ion mobility spectrometry, we also have a convenient method of looking at higher order structure. Our recently introduced SYNAPT ^TM HDMS ^TM System allows different conformations of the same protein to be distinguished. This new technology enables the analysis of samples differentiated by size and shape, as well as mass, to deliver increased specificity and sample definition. Helping our customers to fully understand their product is one of our key objectives and will allow them to move forward in implementing risk-based approaches to engineering their products.

We have responded quickly to the need to continually monitor biotherapeutic product quality, with a new approach to system qualification. To be effective, methods need to generate accurate results day-in, day-out. With this is mind, we have developed turnkey solutions that incorporate not only quality-control tested columns, reagents, and eluents, but also installation, operation, and performance qualification protocols that ensure every aspect of the system is performing. This allows our customers to generate reproducible results, routinely, and obtain the same results whether their labs are based in Europe or around the world.

Another issue for many analytical labs working in biotherapeutic quality is how to reduce the time required for processing and annotating LC/MS data. We have found that this is a major factor affecting productivity, so earlier this year Waters introduced new software dedicated to the processing of biopharmaceutical LC/MS data, incorporating functionality specific to protein and peptide analysis. This is another example where we have taken the advice of our customers and collaborators in optimising a product, which is already making a huge impact in labs in Europe as well as around the world.

With the move towards better process control and optimization, labs are also showing a growing interest in our tools for multivariate analysis of LC/MS data. The ability to interpret data in a meaningful way can help our customers make intelligent decisions about their processes. I would certainly expect to see this approach more widely adopted over the next few years.

NGP: As in other industries facing such competition, time to market is critical and there is a constant need to speed up analyses and generate results faster. How does Waters approach the need to improve efficiency in the lab?
MH: Remember that it's not only reduced run times that will improve efficiency. Reliable sample preparation, reproducible data, automated data processing and system up-time, amongst other factors, will play a part. We focus on all these areas in designing systems which are fit-for-purpose in the biopharmaceutical lab; the specialisation in our Chemistry Operations, Instrumentation and Informatics divisions has helped us significantly in realising the analytical platforms that we have today.

NGP: In your view, what have been the advances in analytical technologies from Waters that have most significantly impacted the industry?
MH: Our ACQUITY UPLC ® System platform is a classic example of a "disruptive" technology that has reshaped the liquid chromatography industry with extremely positive results. As a standalone system, UPLC ® brings the benefits of shorter run times, better resolution and higher sensitivity, but when incorporated into a true application-based system solution, we have a really powerful approach to offer to our customers. We now have UPLC Technology-based system solutions for the analysis of amino acids, peptides, and oligos and our customers benefit from a large support network, easy method transfer protocols, and thousands of ready-to-run methods. Due to the complexity of biopharmaceutical analyses and the higher degree of potential variability encountered, we been working towards providing customers with a higher degree of predictability and certainty to generated results, and I believe we have successfully achieved this. For me, the Waters UPLC Amino Acid Analysis Solution is a great example of where chemistries, hardware, software, validation tools and applications expertise have been combined into a single package to produce fundamentally better results.

In March this year, we introduced the PATROL ^TM UPLC Process Analyzer, a new system enabling quantifiable, real-time, in-process analysis directly on the manufacturing floor. LC has not previously been adopted as a PAT technique as the run times required for good resolution are unacceptably long. However, with UPLC we can reduce hour-long runs down to minutes so that analyses can be deployed in the manufacturing environment. Many of our customers, in traditional small molecule and in biopharmaceutical companies, have already deployed UPLC for process monitoring and cleaning validation. The development of this new system will go a step further in improving manufacturing efficiency.

Our SYNAPT HDMS system is another example of a platform that has changed the way our customers work. Obtaining three-dimensional information on proteins was very difficult to do using existing mass spectrometric-based techniques so this technology has opened new avenues of protein structure investigation. Other applications of this technology are saving our customers significant time and money in product development, for example, in pegylated protein analysis. Although PEG is the cheapest component of a final product, it can have a profound effect on the efficacy of the drug and the quality of the therapy, so the ability to quality control batches of PEG is extremely important for the industry. The application of this technology has saved companies millions of dollars in preventing the waste of valuable product. Previously they had no means of determining which batches of PEG would be suitable for conjugation to their therapeutic protein, resulting in a wide variation in quality and efficacy. Now, using the ion mobility technology built into SYNAPT HDMS, they can select the batches of PEG that will deliver the highest yield of final therapeutic product, so this has made a huge impact on their business. This is just one example, but we are continually identifying ways in which this breakthrough technology can answer complex questions.

And although it has been only recently released, our BiopharmaLynx ^TM Software is also having a significant difference in the way our customers work. We look forward to seeing the larger impact of this customized software solution over the next couple of years.

NGP: Speaking of software, how relevant is Waters' larger portfolio of informatics products to the biopharmaceutical industry?
MH: Very. Bioinformatics is playing an increasingly important role in understanding complex information. In fact, the specifications of an instrument are taking a back seat to system suitability and data processing software: Generating accurate results reproducibly, and being able to reliably process and interpret the data is now more important to our customers. In addition, informatics for data/knowledge sharing is important. All the key data generated in the development of a drug needs to be made instantly available to everyone working on the project. Tools for knowledge sharing are a vital resource for capturing and sharing ideas and thought processes.

NGP: What have been the keys to Waters' success in this market segment?
MH: Our success has largely resulted from our efforts to thoroughly understand the market and to focus resources in product development and applications development. We have made a long-term commitment to developing products for biotherapeutic analysis and have benefited from good references and a reputation for providing innovative technologies. Our local application and service support is a key differentiator for us; our service organisation recently received an excellence award for global services delivery and technical support.

NGP: With the range of potential biotech drug candidates expanding to include antibody fragments, next generation vaccines etc., where will Waters be focusing in developing the next generation of analytical instrumentation and applications?
MH: We will do whatever it takes to make our customers successful. By identifying and responding to the common pressures faced by our customers we will continue to make a difference.

As a n important objective over the coming months , we look to leverage UPLC technology in other modes of chromatography to improve analytical resolution, speed, and sensitivity, and thus further advance detection and characterisation by LC/MS. We will continue to develop our electrospray time-of-flight mass spectrometry products to have a greater impact on the biopharmaceutical market, and also continue our informatics innovations for greater levels of productivity and compliance. Labs are driven by accurate, meaningful results - so workflow is, and will continue to be, a very important focus for us.

Mike Harrington, Vice President of Waters European Operations, began his career with Waters in 1987 after completing his Ph.D. in Biochemistry from Trinity College, Dublin. He worked in the UK for Millipore/Waters as a Sales Representative, Regional Sales Manager, and National Sales Manager. In 1996, Mike became the General Manager of the newly-acquired Phase Separations business in the UK. After moving to the U.S. in 1998, Mike served as the Director of US Chemistry Sales, and later as the Senior Director of Waters US Sales Operations. In 2006, Mike returned to Europe in his current role, based at Waters European Headquarters, near Paris.